Gene Therapy for Lymphoma in HIV Patients

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AIDS Malignancy Consortium

Must be taking: Anti-HIV regimen

Disqualifiers: Active CNS disease, Myeloproliferative disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy for individuals with HIV-related lymphoma that hasn't responded to treatment or has returned after initial improvement. The goal is to determine the best dose and study side effects while enhancing the immune system's resistance to HIV-1. The treatment involves adding special anti-HIV genes to stem cells, potentially strengthening the body's defense against the virus. This trial suits individuals with certain types of lymphoma who are living with HIV and undergoing specific anti-HIV treatments.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

Participants must switch from zidovudine (AZT) and efavirenz to an alternative HIV regimen at least two weeks before the transplant. Other medications are not specifically mentioned, so it's best to discuss with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the gene therapy in this study uses a special virus and certain anti-HIV genes to help the patient's immune cells combat HIV. Previous studies have found that this type of gene therapy can create lasting changes in the blood, with effects persisting up to two years after treatment. Importantly, the therapy has undergone safety testing, and researchers are examining any side effects and determining the optimal dose.

As this is an early-stage trial, evidence about safety is still being gathered. However, reaching this stage indicates that initial tests have shown the treatment is generally well-tolerated. Safety remains a top priority, and researchers will closely monitor participants for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike standard treatments for lymphoma in HIV patients, which often involve chemotherapy and antiretroviral therapy, this new approach uses gene therapy to tackle the disease. The treatment is unique because it involves modifying the patient's own stem cells with a lentivirus vector that introduces a combination of CCR5 shRNA, TRIM5alpha, and a TAR decoy to help the immune system fight both lymphoma and HIV. Researchers are excited because this method could potentially provide a dual benefit: controlling the lymphoma while simultaneously offering resistance to HIV, something no current treatment can do.

What evidence suggests that this gene therapy might be an effective treatment for HIV-related lymphoma?

Research shows that the gene therapy studied in this trial helps immune cells resist HIV. Earlier studies demonstrated that the method used in this therapy protects new immune cells from HIV infection. This trial uses specially altered stem cells to introduce anti-HIV genes into the body, which can remain active for up to two years. Early results suggest that this method effectively delivers protective genes to human cells. These findings indicate that the treatment could help patients with HIV-related lymphoma by boosting their immune system against HIV. ^{1 2 3 4 5}

Who Is on the Research Team?

Mehrdad Abedi

Principal Investigator

AIDS Malignancy Consortium

Are You a Good Fit for This Trial?

Adults over 18 with HIV-related lymphomas that have relapsed or didn't respond to treatment, who are now receiving a stem cell transplant. They must be on stable antiretroviral therapy, have good organ function and performance status, and agree to use contraception. Excluded are those with severe health issues like dementia, uncontrolled infections, recent heart problems, or other cancers.

Inclusion Criteria

My kidney function, measured by creatinine, is within normal limits.

You are expected to live for at least 3 more months.

I have a confirmed diagnosis of Hodgkin's lymphoma within the last 8 months.

Exclusion Criteria

I do not have any active infections.

I haven't had heart issues like heart attack, irregular heartbeat, or heart failure in the last 6 months.

I have had a seizure in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Conditioning

Patients receive BEAM or BEAM-R regimen as standard of care, including carmustine, cytarabine, etoposide, and melphalan, with rituximab for B-cell lymphoma patients.

6 days

Daily visits for chemotherapy administration

Transplant and Gene Therapy

Patients undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells.

1 day

1 visit (in-person)

Post-transplant Monitoring

Patients are monitored for engraftment and safety, including hematologic function and CD4 recovery.

3 months

Frequent visits at days 7, 14, 21, 28, 42, 60, 90

Long-term Follow-up

Participants are monitored for safety, efficacy, and persistence of gene-modified cells, with assessments up to 15 years.

15 years

Yearly visits after initial frequent follow-ups

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Hematopoietic Stem Cell Transplantation
• Carmustine
• Cytarabine
• Etoposide
• Laboratory Biomarker Analysis
• Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy-transduced Autologous CD34-positive Hematopoietic Progenitor Cells
• Melphalan
• Peripheral Blood Stem Cell Transplantation

Trial Overview The trial is testing gene therapy using 'anti-HIV genes' in stem cells for patients with HIV-related lymphoma undergoing stem cell transplants. The aim is to make immune cells resistant to HIV-1 infection. It includes lab analysis of biomarkers and various chemotherapy drugs alongside the transplantation procedure.

How Is the Trial Designed?

Group I: Treatment (anti-HIV gene transduced CD34+ cells) Experimental Treatment 8 Interventions

Patients receive BEAM regimen administered as standard of care comprising carmustine on day -6, cytarabine BID on days -5 to -2, etoposide BID on days -5 to -2, and melphalan on day -1. Patients undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells over 1 hour.

Who Is Running the Clinical Trial?

AIDS Malignancy Consortium

Lead Sponsor

Trials

64

Recruited

9,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Citations

1. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/782403

lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy- ... Upon transfer of the lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive HPCs into the patient, the HPCs are resistant to HIV ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02797470

Study Details | NCT02797470 | Gene Therapy in Treating ... This phase I/II trial studies the side effects and best dose of gene therapy in treating patients with human immunodeficiency virus (HIV)-related lymphoma

3. synapse.patsnap.com synapse.patsnap.com/drug/8e7882bcc2be49a08ee306a5021ab2ae

Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy- ... Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy-transduced Autologous CD34-positive HPCs(NCI): a Gene transference Drug, Initially developed by National ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3130552/

RNA-based gene therapy for HIV with lentiviral vector ... Stem cell gene therapy for HIV results in sustained RNA expression in the blood of patients for up to 2 years following transplant.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2329050116300663

Preclinical safety and efficacy of an anti–HIV-1 lentiviral ... We demonstrate here the effective delivery of LVsh5/C46 to human T cell lines, peripheral blood mononuclear cells, primary CD4+ T lymphocytes, and CD34+ ...